Recombinant Viral Polytope for Neoepitope Presentation

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Solution Overview

Problem

Current methods for identifying and delivering neoepitopes in cancer immunotherapy face challenges due to the large number of possible targets, variability in antigen processing, and unpredictability of therapeutic success, leading to suboptimal immune responses.

Innovation Solution

Development of recombinant viral expression systems that combine selected neoepitopes with trafficking signals to enhance antigen processing and presentation, using adenoviral vectors with E1 and E2b genes deleted, and incorporating co-stimulatory molecules and immune stimulatory cytokines to maximize therapeutic effect.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple neoepitopes are delivered to antigen presenting cells, then the number of potential targets increases, but the unpredictability of therapeutic success increases due to variability in antigen processing

Engineering Contradiction:

Improvenumber of potential targetsVSAvoidpredictability of therapeutic success

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the parameter of neoepitope delivery by using recombinant viral expression systems that control the expression, processing, and presentation of neoepitopes through defined biological pathways, thereby increasing predictability while maintaining multiple targets

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses antigen presenting cells as intermediaries that are engineered to process and present multiple neoepitopes through controlled expression systems, mediating between the neoepitope delivery and the immune response to improve predictability

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If neoepitopes are filtered by mutation type, transcription level, and HLA binding, then the number of potential targets is reduced, but the likelihood of therapeutic success increases

Engineering Contradiction:

Improvelikelihood of therapeutic successVSAvoidnumber of potential targets

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments the neoepitope selection process into distinct filtering stages (mutation type, transcription level, HLA binding) to systematically identify the most promising targets while maintaining a manageable number of candidates for further development

Inventive Principle:

Principle #1Segmentation

3Reliability

If recombinant viral expression systems with trafficking signals are used, then antigen processing and presentation is improved, but the device complexity increases

Engineering Contradiction:

Improveantigen processing and presentationVSAvoidexpression system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs trafficking signals that enable the recombinant viral expression system to automatically direct neoepitopes to appropriate sub-cellular locations through inherent cellular machinery, improving antigen processing without requiring external intervention or complex additional components

Inventive Principle:

Principle #25Self-service

Data Source

PatentUS11154597B2Sequence arrangements and sequences for neoepitope presentation

Publication Date: 2021.10.26 NANT HOLDINGS IP LLC

AI summary

Systems and methods are presented that allow for selection of tumor neoepitopes that are then used to generate a recombinant polytope that is optimized for proper trafficking and processing. In preferred methods, the polytope is encoded in a viral expression system that is used as a therapeutic agent.